Ketamine's rapid and sustained antidepressant effects are driven by distinct mechanisms.
Cellular and molecular life sciences : CMLS February 27, 2024 Radhika Rawat, Elif Tunc-Ozcan, Sara Dunlop et al. 17 citations
Ketamine's rapid and sustained antidepressant effects rely on separate biological mechanisms. A single dose rapidly improves mood by increasing activity of immature neurons in the hippocampal dentate gyrus without generating new neurons. Six doses over two weeks doubled the duration of behavioral improvement, which correlated with increased numbers of immature neurons (neurogenesis) and reduced bone morphogenetic protein (BMP) signaling, a known inhibitor of neurogenesis. Experimentally maintaining BMP signaling with a lentivirus blocked the sustained but not the rapid effects, showing that decreased BMP signaling and increased neurogenesis are necessary for ketamine's long-lasting benefits. Understanding these dual mechanisms may aid development of safer, sustained antidepressant therapies.